The NIEHS knock out core (KOC) is a service orientated facility, which aims at helping investigators at NIEHS develop animal models to further their research and fulfilling the mission statement of NIEHS. The KOC aids investigators in generating transgenic mouse models specific for their research needs; including traditional knockouts, conditional knockouts, and knock-ins. It also provides assistance in establishing mutant cell lines for in vitro studies, dissecting early stage embryos, and establishing genotyping strategies for both novel mouse lines and existing lines. Each project in the core is a long-term commitment, and numerous projects are at different stages of completion at any given time of the year. The core typically works closely with investigators from project inception, which starts with meeting with the PI's group to determine not only technical aspects of the proposed project but also to provide scientific guidance in generating the most appropriate mouse model. The KOC recently hired a molecular geneticist to aid investigators that lack expertise in generating targeting vectors and developing screening strategies. With the increased personnel, the KOC has been able to generate transgenic mouse lines using the ROSA26 locus with substantial success. This has been done through conventional homologous recombination and recombinase mediated cassette exchange (RMCE), which allows for insertion of single copy transgenes into the ROSA26 locus. Although the KOC is focused on the scientific support of investigators at the institute, this is done with financial consideration, which includes exploiting the ROSA26 locus to generate classic transgene mouse lines in-house, being available to meet with investigators to optimize mouse breeding strategies, and overseeing complex mouse colonies such as the COX-2 colony.